In conscious dogs with systolic heart failure, a 24-hour infusion of omecamtiv mecarbil significantly increased stroke volume (44+/-6.5%) and cardiac output (22+/-2.8%) without increasing MVO2.
Does omecamtiv mecarbil improve cardiac function in conscious dogs with systolic heart failure?
Omecamtiv mecarbil improves left ventricular systolic function in canine models of heart failure without increasing myocardial oxygen consumption, unlike traditional inotropes.
p-value: p=<0.05
BACKGROUND: Therapy for chronic systolic heart failure (sHF) has improved over the past 2 decades, but the armamentarium of drugs is limited and consequently sHF remains a leading cause of death and disability. In this investigation, we examined the effects of a novel cardiac myosin activator, omecamtiv mecarbil (formerly CK-1827452) in 2 different models of heart failure. METHODS AND RESULTS: Two different models of sHF were used: (1) pacing-induced sHF after myocardial infarction (MI-sHF) and (2) pacing-induced sHF after 1 year of chronic pressure overload left ventricular hypertrophy (LVH-sHF). Omecamtiv mecarbil increased systolic function in sHF dogs, chronically instrumented to measure LV pressure, wall thickness, and cardiac output. Omecamtiv mecarbil, infused for 24 hours, induced a sustained increase without desensitization (P<0.05) in wall thickening (25+/-6.2%), stroke volume (44+/-6.5%) and cardiac output (22+/-2.8%), and decreased heart rate (15+/-3.0%). The major differences between the effect of omecamtiv mecarbil on cardiac function and the effect induced by a catecholamine, for example, dobutamine, is that omecamtiv mecarbil did not increase LV dP/dt but rather increased LV systolic ejection time by 26+/-2.9% in sHF. Another key difference is that myocardial O(2) consumption (MVO(2)), which increases with catecholamines, was not significantly affected by omecamtiv mecarbil. CONCLUSIONS: These results demonstrate that chronic infusion of the cardiac myosin activator, omecamtiv mecarbil, improves LV function in sHF without the limitations of progressive desensitization and increased MVO(2.) This unique profile may provide a new therapeutic approach for patients with sHF.
Shen et al. (Tue,) conducted a other in Systolic heart failure. Omecamtiv mecarbil vs. Dobutamine (mechanistic comparison) was evaluated on Systolic function (wall thickening, stroke volume, cardiac output, heart rate) (p=<0.05). In conscious dogs with systolic heart failure, a 24-hour infusion of omecamtiv mecarbil significantly increased stroke volume (44+/-6.5%) and cardiac output (22+/-2.8%) without increasing MVO2.